tbuckley/cabot-search huggingface dataset:
Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B
Authors: Dong Ji, Yan Chen, Jingfeng Bi, Qinghua Shang, Huabao Liu, Jia-Bo Wang, Lin Tan, Jing Wang, Yongping Chen, Qin Li, Qinghua Long, Laicheng Song, Li Jiang, Guangming Xiao, Zujiang Yu, Liang Chen, Xiaodong Wang, Da Chen, Zhiqin Li, Zheng Dong, Yongping Yang
Journal: Journal of Hepatology (2022)

Chronic hepatitis B (CHB) and liver fibrosis are associated with a high risk of hepatocellular carcinoma (HCC) development. We assessed whether entecavir (ETV) plus Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine, can further reduce the risk of HCC in treatment-naïve Chinese patients with CHB and an Ishak fibrosis score of ≥3 points derived from our parent double-blind randomized placebo-controlled trial.After a 72-week comparison between ETV+BRC and ETV+placebo treatment, participants were eligible to enter an open-label treatment phase and were followed up every 6 months. The primary [secondary] endpoints were the incidence of HCC [liver-related deaths, non-HCC events, and non-liver-related deaths]. Modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP) populations were defined for the time-to-event analysis.A total of 1,000 patients were recruited; the median age was 42.0 years; 69.9% were male and 58.3% were HBeAg positive. In the mITT population, the 7-year cumulative incidence of HCC [liver-related deaths] was 4.7% [0.2%] for ETV+BRC, which was significantly lower than 9.3% [2.2%] for ETV monotherapy (p = 0.008 [p = 0.030]). Notably, ETV+BRC treatment yielded a lower incidence of HCC in those who did not achieve regression of fibrosis at week 72 than ETV monotherapy (p = 0.018). There were no differences in the other 2 secondary endpoints or safety profiles between the groups. Multivariable Cox proportional regression analysis, including the treatment allocation as a parameter, also demonstrated that ETV+BRC treatment was associated with a reduced incidence of HCC. The ITT and PP analyses showed consistent results.ETV plus BRC combination treatment could further reduce the risk of HCC and liver-related deaths in patients with CHB and advanced fibrosis or cirrhosis, which may have important clinical implications for HCC prevention.Patients with chronic hepatitis B virus infection are at an increased risk of developing liver cancer (specifically hepatocellular carcinoma [HCC]). While there are effective antiviral treatments that can suppress the virus in chronically infected patients, the risk of HCC remains. Herein, we show that adding a traditional Chinese medicine called Biejia-Ruangan compound to an antiviral reduced the risk of HCC in patients with chronic hepatitis B.
Efficacy of CD40 Agonists Is Mediated by Distinct cDC Subsets and Subverted by Suppressive Macrophages
Authors: Aleksandar Murgaski, Máté Kiss, Helena Van Damme, Daliya Kancheva, Isaure Vanmeerbeek, Jiri Keirsse, Eva Hadadi, Jan Brughmans, Sana M. Arnouk, Ahmed E.I. Hamouda, Ayla Debraekeleer, Victor Bosteels, Yvon Elkrim, Louis Boon, Sabine Hoves, Niels Vandamme, Sofie Deschoemaeker, Sophie Janssens, Abhishek D. Garg, Greetje Vande Velde, Martina Schmittnaegel, Carola H. Ries, Damya Laoui
Journal: Cancer Research (2022)

Abstract Agonistic αCD40 therapy has been shown to inhibit cancer progression in only a fraction of patients. Understanding the cancer cell–intrinsic and microenvironmental determinants of αCD40 therapy response is therefore crucial to identify responsive patient populations and to design efficient combinatorial treatments. Here, we show that the therapeutic efficacy of αCD40 in subcutaneous melanoma relies on preexisting, type 1 classical dendritic cell (cDC1)–primed CD8+ T cells. However, after administration of αCD40, cDC1s were dispensable for antitumor efficacy. Instead, the abundance of activated cDCs, potentially derived from cDC2 cells, increased and further activated antitumor CD8+ T cells. Hence, distinct cDC subsets contributed to the induction of αCD40 responses. In contrast, lung carcinomas, characterized by a high abundance of macrophages, were resistant to αCD40 therapy. Combining αCD40 therapy with macrophage depletion led to tumor growth inhibition only in the presence of strong neoantigens. Accordingly, treatment with immunogenic cell death–inducing chemotherapy sensitized lung tumors to αCD40 therapy in subcutaneous and orthotopic settings. These insights into the microenvironmental regulators of response to αCD40 suggest that different tumor types would benefit from different combinations of therapies to optimize the clinical application of CD40 agonists. Significance: This work highlights the temporal roles of different dendritic cell subsets in promoting CD8+ T-cell–driven responses to CD40 agonist therapy in cancer.
Role of thermogenic adipose tissue in lipid metabolism and atherosclerotic cardiovascular disease: lessons from studies in mice and humans
Authors: Zhixiong Ying, Naomi Tramper, Enchen Zhou, Mariëtte R Boon, Patrick C N Rensen, Sander Kooijman
Journal: Cardiovascular Research (2022)

Brown adipocytes within brown adipose tissue (BAT) and beige adipocytes within white adipose tissue dissipate nutritional energy as heat. Studies in mice have shown that activation of thermogenesis in brown and beige adipocytes enhances the lipolytic processing of triglyceride-rich lipoproteins (TRLs) in plasma to supply these adipocytes with fatty acids for oxidation. This process results in formation of TRL remnants that are removed from the circulation through binding of apolipoprotein E (ApoE) on their surface to the LDL receptor (LDLR) on hepatocytes, followed by internalization. Concomitantly, lipolytic processing of circulating TRLs leads to generation of excess surface phospholipids that are transferred to nascent HDLs, increasing their capacity for reverse cholesterol transport. Activation of thermogenic adipocytes thus lowers circulating triglycerides and non-HDL-cholesterol, while it increases HDL-cholesterol. The combined effect is protection from atherosclerosis development, which becomes evident in humanized mouse models with an intact ApoE-LDLR clearance pathway only, and is additive to the effects of classical lipid-lowering drugs including statins and proprotein convertase subtilisin/kexin type 9 inhibitors. A large recent study revealed that the presence of metabolically active BAT in humans is associated with lower triglycerides, higher HDL-cholesterol and lower risk of cardiovascular diseases. This narrative review aims to provide leads for further exploration of thermogenic adipose tissue as a therapeutic target. To this end, we describe the latest knowledge on the role of BAT in lipoprotein metabolism and address, for example, the discovery of the β2-adrenergic receptor as the dominant adrenergic receptor in human thermogenic adipocytes.
Are Pivotal Clinical Trials for Drugs Approved for Leukemias and Multiple Myeloma Representative of the Population at Risk?
Authors: Mycal Casey, Lorriane Odhiambo, Nidhi Aggarwal, Mahran Shoukier, Jamani Garner, K.M. Islam, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2022)

There are significant disparities in care and outcomes for patients with leukemias and multiple myeloma (MM). To evaluate the extent to which clinical trials (CTs) match the demographic and geographic diversity of populations affected by leukemias and MM.CTs leading to drug approval were identified from the US Food and Drug Administration databases. Demographic and geographic data were collected from ClinicalTrials.gov and primary manuscripts. Standard descriptive statistics were used to summarize the data in frequencies and proportions, including 95% CIs, by race, ethnicity, sex, and malignancy subtypes.A total of 41 (67.2%) trials leading to drug approval reported data on race and 20 (48.8%) on ethnicity. These trials included 13,731 patients, of whom 11,209 (81.6%) were White. Among minorities, Asian-Pacific Islanders and Blacks had the highest representation in chronic myeloid leukemia, 147 (12.7%) and 61 (5.3%), and lowest in chronic lymphocytic leukemia, 55 (3%) and 20 (1.1%), respectively. Proportions for Blacks, Native Americans, and Hispanics were significantly low, reflecting under-representation in trials compared with the proportion in the general population. Females were also under-represented in acute myeloid leukemia (44.7% v 60.5%, P < .0001), and males in MM (55.3% v 60.2%, P < .0001) and chronic myeloid leukemia (55.2% v 62.9%, P < .0001). The geographic distribution of trials showed inadequate regional and state participation compared with mortality for all malignancies except MM.There are significant demographic and geographic under-representation and imbalances in pivotal CTs leading to drug approvals for leukemias and MM compared with the population affected. These disparities need to be addressed to make results applicable to all relevant populations.
Monkeypox self-diagnosis abilities, determinants of vaccination and self-isolation intention after diagnosis among MSM, the Netherlands, July 2022
Authors: Haoyi Wang, Kennedy J.I. d'Abreu de Paulo, Thomas Gültzow, Hanne M.L. Zimmermann, Kai. J. Jonas
Journal: Eurosurveillance (2022)

Monkeypox is a zoonotic disease and leads to a smallpox-like disease in humans. The current epidemic in European countries requires informed responses. We investigated the ability to self-diagnose a potential infection, and determinants of vaccination and self-isolation intention after diagnosis among 394 MSM in the Netherlands. We found that about half were able to self-diagnose monkeypox, that 70% had a high intention to get vaccinated and 44% to self-isolate after monkeypox diagnosis. Determinants went beyond mere risk behaviour criteria.
Seroprevalence of antibodies against SARS-CoV-2 and risk of COVID-19 in Navarre, Spain, May to July 2022
Authors: Jesús Castilla, Óscar Lecea, Carmen Martín Salas, Delia Quílez, Ana Miqueleiz, Camino Trobajo-Sanmartín, Ana Navascués, Iván Martínez-Baz, Itziar Casado, Cristina Burgui, Nerea Egüés, Guillermo Ezpeleta, Carmen Ezpeleta
Journal: Eurosurveillance (2022)

In Navarre, Spain, in May 2022, the seroprevalence of anti-nucleocapsid (N) and anti-spike (S) antibodies of SARS-CoV-2 was 58.9% and 92.7%, respectively. The incidence of confirmed COVID-19 thereafter through July was lower in people with anti-N antibodies (adjusted odds ratio (aOR) = 0.08; 95% confidence interval (CI): 0.05-0.13) but not with anti-S antibodies (aOR = 1.06; 95% CI: 0.47-2.38). Hybrid immunity, including anti-N antibodies induced by natural exposure to SARS-CoV-2, seems essential in preventing Omicron COVID-19 cases.
Recording of ’COVID-19 vaccine declined‘: a cohort study on 57.9 million National Health Service patients’ records in situ using OpenSAFELY, England, 8 December 2020 to 25 May 2021
Authors: Helen J Curtis, Peter Inglesby, Brian MacKenna, Richard Croker, William J Hulme, Christopher T Rentsch, Krishnan Bhaskaran, Rohini Mathur, Caroline E Morton, Sebastian CJ Bacon, Rebecca M Smith, David Evans, Amir Mehrkar, Laurie Tomlinson, Alex J Walker, Christopher Bates, George Hickman, Tom Ward, Jessica Morley, Jonathan Cockburn, Simon Davy, Elizabeth J Williamson, Rosalind M Eggo, John Parry, Frank Hester, Sam Harper, Shaun O’Hanlon, Alex Eavis, Richard Jarvis, Dima Avramov, Paul Griffiths, Aaron Fowles, Nasreen Parkes, Stephen JW Evans, Ian J Douglas, Liam Smeeth, Ben Goldacre
Journal: Eurosurveillance (2022)

Background Priority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined. Aim We describe records of COVID-19 vaccines being declined, according to clinical and demographic factors. Methods With the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or ’at risk’. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices. Results Of 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587; 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation. Conclusions Clinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.
The relevance of multiple clinical specimens in the diagnosis of monkeypox virus, Spain, June 2022
Authors: Cristina Veintimilla, Pilar Catalán, Roberto Alonso, Darío García de Viedma, Laura Pérez-Lago, María Palomo, Alejandro Cobos, Teresa Aldamiz-Echevarria, Patricia Muñoz
Journal: Eurosurveillance (2022)

A monkeypox virus (MPXV) outbreak has been ongoing worldwide since May 2022. The role of specimens other than skin lesions for MPXV diagnosis is unknown. We evaluated 140 different clinical specimens by real-time PCR. The highest positivity rates (97%) were from skin lesions of any part of the body, followed by plasma, pharyngeal and anal swabs. Testing specimens from multiple sites may improve the sensitivity and reduce false-negative test results.
Role of population and test characteristics in antigen-based SARS-CoV-2 diagnosis, Czechia, August to November 2021
Authors: Tomáš Kliegr, Jiří Jarkovský, Helena Jiřincová, Jaroslav Kuchař, Tomáš Karel, Ruth Tachezy
Journal: Eurosurveillance (2022)

BackgroundAnalyses of diagnostic performance of SARS-CoV-2 antigen rapid diagnostic tests (AG-RDTs) based on long-term data, population subgroups and many AG-RDT types are scarce.AimWe aimed to analyse sensitivity and specificity of AG-RDTs for subgroups based on age, incidence, sample type, reason for test, symptoms, vaccination status and the AG-RDT's presence on approved lists.MethodsWe included AG-RDT results registered in Czechia's Information System for Infectious Diseases between August and November 2021. Subpopulations were analysed based on 346,000 test results for which a confirmatory PCR test was recorded ≤ 3 days after the AG-RDT; 38 AG-RDTs with more than 100 PCR-positive and 300 PCR-negative samples were individually evaluated.ResultsAverage sensitivity and specificity were 72.4% and 96.7%, respectively. We recorded lower sensitivity for age groups 0-12 (65.5%) and 13-18 years (65.3%). The sensitivity level rose with increasing SARS-CoV-2 incidence from 66.0% to 76.7%. Nasopharyngeal samples had the highest sensitivity and saliva the lowest. Sensitivity for preventive reasons was 63.6% vs 86.1% when testing for suspected infection. Sensitivity was 84.8% when one or more symptoms were reported compared with 57.1% for no symptoms. Vaccination was associated with a 4.2% higher sensitivity. Significantly higher sensitivity levels pertained to AG-RDTs on the World Health Organization Emergency Use List (WHO EUL), European Union Common List and the list of the United Kingdom's Department of Health and Social Care.ConclusionAG-RDTs from approved lists should be considered, especially in situations associated with lower viral load. Results are limited to SARS-CoV-2 delta variant.
Science and beyond science in the reporting of quality of facility-based maternal and newborn care during the COVID-19 pandemic—Authors’ reply
Authors: Marzia Lazzerini, Raquel Costa, Ilaria Mariani, Eline Skirnisdottir Vik, Helen Elden, Karolina Linden, Mehreen Zaigham, Alina Liepinaitienė, Maryse Arendt, Zalka Drglin, Emma Sacks, Ornella Lincetto, Emanuelle Pessa Valente
Journal: The Lancet Regional Health - Europe (2022)
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
Authors: Ferran Nadeu, Romina Royo, Ramon Massoni-Badosa, Heribert Playa-Albinyana, Beatriz Garcia-Torre, Martí Duran-Ferrer, Kevin J. Dawson, Marta Kulis, Ander Diaz-Navarro, Neus Villamor, Juan L. Melero, Vicente Chapaprieta, Ana Dueso-Barroso, Julio Delgado, Riccardo Moia, Sara Ruiz-Gil, Domenica Marchese, Ariadna Giró, Núria Verdaguer-Dot, Mónica Romo, Guillem Clot, Maria Rozman, Gerard Frigola, Alfredo Rivas-Delgado, Tycho Baumann, Miguel Alcoceba, Marcos González, Fina Climent, Pau Abrisqueta, Josep Castellví, Francesc Bosch, Marta Aymerich, Anna Enjuanes, Sílvia Ruiz-Gaspà, Armando López-Guillermo, Pedro Jares, Sílvia Beà, Salvador Capella-Gutierrez, Josep Ll. Gelpí, Núria López-Bigas, David Torrents, Peter J. Campbell, Ivo Gut, Davide Rossi, Gianluca Gaidano, Xose S. Puente, Pablo M. Garcia-Roves, Dolors Colomer, Holger Heyn, Francesco Maura, José I. Martín-Subero, Elías Campo
Journal: Nature Medicine (2022)

Abstract Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS) high –B cell receptor (BCR) low -signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT.
“Normative data for multiple breath washout outcomes in school-aged Caucasian children.” Pinelopi Anagnostopoulou, Philipp Latzin, Renee Jensen, <i>et al. Eur Respir J</i> 2020; 55: 1901302.
Journal: European Respiratory Journal (2022)

The aforementioned study provided normative data for multiple breath washout outcomes in school-aged Caucasian children measured with the Exhalyzer D device (Eco Medics AG). After publication of this study, an error in the cross-sensitivity correction of the oxygen and carbon dioxide sensors in this device has been identified that leads to an overestimation of MBW outcomes [1]. Correction of this error and reanalysis of MBW data is possible with an updated software version (Spiroware version 3.3.1, Eco Medics AG). The authors of this article present updated normative data corrected for this sensor error in the research letter “Normative multiple breath washout data in school-aged children corrected for sensor error” [2], published in this issue of the European Respiratory Journal .
Circular RNA circFIRRE drives osteosarcoma progression and metastasis through tumorigenic-angiogenic coupling
Authors: Lingfeng Yu, Hao Zhu, Zhen Wang, Jianhao Huang, Yan Zhu, Gentao Fan, Yicun Wang, Xi Chen, Guangxin Zhou
Journal: Molecular Cancer (2022)

Disappointing clinical efficacy of standard treatment has been proven in refractory metastatic osteosarcoma, and the emerging anti-angiogenic regimens are still in the infantile stage. Thus, there is an urgent need to develop novel therapeutic approach for osteosarcoma lung metastasis.circFIRRE was selected from RNA-sequencing of 4 matched osteosarcoma and adjacent samples. The expression of circFIRRE was verified in clinical osteosarcoma samples and cell lines via quantitative real-time polymerase chain reaction (RT-qPCR). The effect of circFIRRE was investigated in cell lines in vitro models, ex vivo models and in vivo xenograft tumor models, including proliferation, invasion, migration, metastasis and angiogenesis. Signaling regulatory mechanism was evaluated by RT-qPCR, Western blot, RNA pull-down and dual-luciferase reporter assays.In this article, a novel circular RNA, circFIRRE (hsa_circ_0001944) was screened out and identified from RNA-sequencing, and was upregulated in both osteosarcoma cell lines and tissues. Clinically, aberrantly upregulated circFIRRE portended higher metastatic risk and worse prognosis in osteosarcoma patients. Functionally, in vitro, ex vivo and in vivo experiments demonstrated that circFIRRE could drive primary osteosarcoma progression and lung metastasis by inducing both tumor cells and blood vessels, we call as "tumorigenic-angiogenic coupling". Mechanistically, upregulated circFIRRE was induced by transcription factor YY1, and partially boosted the mRNA and protein level of LUZP1 by sponging miR-486-3p and miR-1225-5p.We identified circFIRRE as a master regulator in the tumorigenesis and angiogenesis of osteosarcoma, which could be purposed as a novel prognostic biomarker and therapeutic target for refractory osteosarcoma.
The Rise and Fall of Rheumatic Fever
Authors: Alan L. Bisno
Journal: JAMA (1985)

IN THIS week's issue, the editors of<i>JAMA</i>have republished an article that stands clearly as a landmark in modern medical history. The article, which first appeared inThe Journal35 years ago, presents convincing evidence that acute rheumatic fever may be prevented by penicillin therapy for the antecedent streptococcal throat infection. This study and a succeeding one on the same topic published the next year<sup>1</sup>emerged from the famous Streptococcal Disease Laboratory, which functioned at the Fort Warren, Wyo, air force technical training base in the years shortly after the end of World War II. The laboratory, under the leadership of the late Dr Charles H. Rammelkamp, Jr, included among its ranks a number of young investigators destined to make indelible contributions to the field of infectious diseases. Numbered among these were Dr Floyd W. Denny, the senior author of the 1950<i>JAMA</i>article, the late Dr Lewis W.
Motorcycle Injuries to University Students
Authors: Andrea Cracchiolo
Journal: JAMA (1968)

Motorcycle accidents increase each year. The severe injuries they produce have become almost an epidemic. This study focuses attention on injuries incurred by a specific segment of the population, the university student. The cases of all severely injured students requiring hospitalization were reviewed as to etiology and injury. Although 55% of the students at the University of California, drive automobiles and only 6 1/2% use motorcycles, the number of students injured by motorcycles was greater than those injured by automobiles by a ratio of 2:1.
Adjuvant Atezolizumab Holds Its Own in NSCLC
Journal: Cancer Discovery (2022)

According to new data from the phase III IMpower010 trial, adjuvant atezolizumab improves overall survival compared with best supportive care for some patients with operable non-small cell lung cancer. These results build on previous study findings, in which the immune checkpoint inhibitor, given after surgery and adjuvant chemotherapy, was shown to significantly decrease the likelihood of disease progression.